The importance of lipid conjugation on anti-fusion peptides against Nipah virus

Detalhes bibliográficos
Autor(a) principal: Marques, Marta C.
Data de Publicação: 2022
Outros Autores: Lousa, Diana, Silva, Patrícia M., Faustino, André F., Soares, Cláudio M., Santos, Nuno C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/52076
Resumo: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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spelling The importance of lipid conjugation on anti-fusion peptides against Nipah virusNipah virusAntiviralsFusion inhibitorsLipid conjugationPeptides© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Nipah virus (NiV) is a recently emerging zoonotic virus that belongs to the Paramyxoviridae family and the Henipavirus genus. It causes a range of conditions, from asymptomatic infection to acute respiratory illness and fatal encephalitis. The high mortality rate of 40 to 90% ranks these viruses among the deadliest viruses known to infect humans. Currently, there is no antiviral drug available for Nipah virus disease and treatment is only supportive. Thus, there is an urgent demand for efficient antiviral therapies. NiV F protein, which catalyzes fusion between the viral and host membranes, is a potential target for antiviral drugs, as it is a key protein in the initial stages of infection. Fusion inhibitor peptides derived from the HRC-domain of the F protein are known to bind to their complementary domain in the protein's transient intermediate state, preventing the formation of a six-helix bundle (6HB) thought to be responsible for driving the fusion of the viral and cell membranes. Here, we evaluated the biophysical and structural properties of four different C-terminal lipid-tagged peptides. Different compositions of the lipid tags were tested to search for properties that might promote efficacy and broad-spectrum activity. Fluorescence spectroscopy was used to study the interaction of the peptides with biomembrane model systems and human blood cells. In order to understand the structural properties of the peptides, circular dichroism measurements and molecular dynamics simulations were performed. Our results indicate a peptide preference for cholesterol-enriched membranes and a lipid conjugation-driven stabilization of the peptide α-helical secondary structure. This work may contribute for the development of highly effective viral fusion against NiV inhibitors.This work was financially supported by Fundação para a Ciência e a Tecnologia—Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), through projects PTDC/BBB-BQB/3494/2014, PTDC/QUI-BIQ/114774/2009, PTDC/CCI-BIO/28200/2017 and Pest-OE/EQB/LA0004/2011, and by National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), project R01AI114736, lead by Anne Moscona (Columbia University Medical Center, NY, USA). This work was also financially supported by Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT-MCTES. MCM, PMS and DL were supported by FCT-MCTES fellowships SFRH/BPD/118731/2016, SFRH/BD/118413/2016 and SFRH/BPD/92537/2013, respectively.MDPIRepositório da Universidade de LisboaMarques, Marta C.Lousa, DianaSilva, Patrícia M.Faustino, André F.Soares, Cláudio M.Santos, Nuno C.2022-03-29T16:01:14Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/52076engBiomedicines. 2022 Mar 18;10(3):70310.3390/biomedicines100307032227-9059info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:57:04Zoai:repositorio.ul.pt:10451/52076Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:03:12.117965Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The importance of lipid conjugation on anti-fusion peptides against Nipah virus
title The importance of lipid conjugation on anti-fusion peptides against Nipah virus
spellingShingle The importance of lipid conjugation on anti-fusion peptides against Nipah virus
Marques, Marta C.
Nipah virus
Antivirals
Fusion inhibitors
Lipid conjugation
Peptides
title_short The importance of lipid conjugation on anti-fusion peptides against Nipah virus
title_full The importance of lipid conjugation on anti-fusion peptides against Nipah virus
title_fullStr The importance of lipid conjugation on anti-fusion peptides against Nipah virus
title_full_unstemmed The importance of lipid conjugation on anti-fusion peptides against Nipah virus
title_sort The importance of lipid conjugation on anti-fusion peptides against Nipah virus
author Marques, Marta C.
author_facet Marques, Marta C.
Lousa, Diana
Silva, Patrícia M.
Faustino, André F.
Soares, Cláudio M.
Santos, Nuno C.
author_role author
author2 Lousa, Diana
Silva, Patrícia M.
Faustino, André F.
Soares, Cláudio M.
Santos, Nuno C.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Marques, Marta C.
Lousa, Diana
Silva, Patrícia M.
Faustino, André F.
Soares, Cláudio M.
Santos, Nuno C.
dc.subject.por.fl_str_mv Nipah virus
Antivirals
Fusion inhibitors
Lipid conjugation
Peptides
topic Nipah virus
Antivirals
Fusion inhibitors
Lipid conjugation
Peptides
description © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
publishDate 2022
dc.date.none.fl_str_mv 2022-03-29T16:01:14Z
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/52076
url http://hdl.handle.net/10451/52076
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Biomedicines. 2022 Mar 18;10(3):703
10.3390/biomedicines10030703
2227-9059
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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